EORTC trial 11001: distribution of two ¹⁰B‐compounds in patients with squamous cell carcinoma of head and neck, a translational research/phase 1 trial

Abstract

Boron neutron capture therapy (BNCT) provides highly targeted delivery of radiation through the limited spatial distribution of its effects. This translational research/phase I clinical trial investigates whether BNCT might be developed as a treatment option for squamous cell carcinoma of head and neck (SCCHN) relying upon preferential uptake of the two compounds, sodium mercaptoundecahydro‐closo‐dodecaborate (BSH) or L‐para‐boronophenylalanine (BPA) in the tumour. Before planned tumour resection, three patients received BSH and three patients received BPA. The 10B‐concentration in tissues and blood was measured with prompt gamma ray spectroscopy. Adverse effects from compounds did not occur. After BPA infusion the 10B‐concentration ratio of tumour/blood was 4.0 ± 1.7. 10B‐concentration ratios of tumour/normal tissue were 1.3 ± 0.5 for skin, 2.1 ± 1.2 for muscle and 1.4 ± 0.01 for mucosa. After BSH infusion the 10B‐concentration ratio of tumour/blood was 1.2 ± 0.4. 10B‐concentration ratios of tumour/normal tissue were 3.6 ± 0.6 for muscle, 2.5 ± 1.0 for lymph nodes, 1.4 ± 0.5 for skin and 1.0 ± 0.3 for mucosa. BPA and BSH deliver 10B to SCCHN to an extent that might allow effective BNCT treatment. Mucosa and skin are the most relevant organs at risk.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

“…Because a and 7 Li have short range in tissue and they produce dense ionization along their tracks, most radiation effect is local and occurs within the cells that contain boron. Therefore, the success of BNCT depends on a selective uptake of sufficient amounts of 10 B into cancer cells compared with normal tissues. This can be achieved by use of boron carriers that are preferentially taken up by cancer, such as a derivative of phenylalanine, L-boronophenylalanine (L-BPA).…”

“…Hypothetically, this can be achieved by use of BNCT, because head-andneck carcinomas accumulate L-BPA (10). BNCT is usually administered only once or twice, and a high single dose of irradiation is delivered to the target volume within approximately 1 h instead of a time period of 6 to 7 weeks when conventionally fractionated photon radiation therapy is used.…”

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

“…The biodistribution of BSH achieved T/B ratios ranging from 0.9±0.4 to 1.2±0.4, T/N ratios in the range of 0.7±0.1 to 3.6±0.6, and boron levels in the tumor ranged from 0.7 to 84.2 ppm [20,28,32]. Again, this data illustrates that more selective agents are urgently needed.…”

“…Despite the potential of BNCT becoming an alternative (or adjunct) treatment modality for glioblastoma multiforme (GBM) [12][13][14][15][16][17][18][19][20][21][22][23], melanoma brain metastases [12,24], adenocarcinoma liver metastases [25][26][27][28][29][30], hepatocellular carcinoma [31] and recurrent head and neck cancer patients [32][33][34][35][36], only two drugs have been investigated in these BNCT clinical trials: L-boronophenylalanine (BPA) and sodium borocaptate (BSH) [10]. The vast majority of patients diagnosed with the aforementioned malignancies undergo palliative care options.…”

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

“…However, the potential of BNCT to have a targeted tumoricidal effect is limited by the ability of a boronated agent to accumulate specifically in the tumor (ideally T/N > 3). Clinical trial agents BPA and BSH in glioma have suffered from poor tumor selectivity, with T/N ratios of 1.1 – 2.9 for BPA (10, 26, 27) and 0.7 - 3.6 for BSH (28-30). Therefore, in order for the full therapeutic potential of BNCT to be realized, there is an urgent need to develop novel boronated tumor selective compounds.…”